Body fluid is a complex mixture of different cell types and biological particles. Blood, for example, includes plasma and cells (red blood cells, white blood cells, platelets) and the cells occupy about 55% of blood. Plasma is mostly water and it transfers proteins, ions, vitamins, enzymes, hormone, and other chemicals to cells in the body.
Red blood cells are about 6 to 8 μm in size and serve to provide oxygen to cells. White blood cells are about 10 to 13 μm in diameter and they defend the body from disease as a part of an immune system by fighting against foreign virus and bacteria. Platelets are the smallest cells, 1.5 to 3 μm, and they stop bleeding by forming blood clots.
Fluids in addition to blood, such as saliva, tear, urine, cerebral spinal fluid as well as other body fluids in contact with various organs (e.g. lung) contain mixtures of cells and bioparticles. The type and amount of cells and bioparticles that are present in a particular body fluid (e.g. blood) includes information about the health of the organism, and in the case of an infected individual, information about the diagnosis and prognosis of the disease.
In the case of cancer diagnosis and prognosis, tumor cells can exfoliate from solid tumors and transport throughout the body via the blood stream or other body fluids (e.g. lung cancer cells may exfoliate into the fluid in contact with the lung and prostate cancer cells into urine). These circulating tumor cells (CTCs) are present in extremely low concentrations, and their isolation and detection among the other cells present in the fluid is required for diagnosis and prognosis.
Biological cells are often sensitive to local pressure change because cellular membranes are not rigid. In filtering or isolating cells by mechanical exclusion, exposure of the cells to a high pressure environment can cause lysing. Lysis refers to the disintegration, rupturing, or destruction of a cell. With a cell, such a breakdown is caused by damage to the plasma (outer) membrane and subsequent loss of cell content (cytoplasm, organelles, or nucleus) resulting from the physical insult to the cell.
Because the cellular membranes of biological cells are not rigid, they are highly susceptible to deformation and damage in the process of physical exclusion or separation. This is a particularly difficult problem in isolating rare cells, because a large volume of biofluid must be processed to collect a statistically significant number of rare cells. As fluidic throughput increases, the velocity of the flow (and also of the suspended cells) typically increases, and potentially subjecting the cells to harsh collision with morphological features intended to exclude. Cellular damage can lead to a high rate of false-negative in disease diagnosis or prognosis; this issue must be mitigated or prevented in order to accurately quantify rare cells.